Introduction ! Magnolol (M; l " Fig. 1) is a polyphenolic lignan in the bark of Magnolia officinalis Rehhder & E. Wil- son (Magnoliaceae), which is a frequently pre- scribed Chinese herb for the treatment of anxiety, fever, headache, and neurosis [1]. Various benefi- cial activities of M have been reported, including anti-inflammation [2–5], anticancer [6–9], anti- biotic [5, 10, 11], antispasmodic [12], and antide- pression effects [13, 14]. Most of the in vitro bio- activities of M reported were mainly of the parent form. Nonetheless, in the analysis of the biological fate of polyphenols, it has been increasingly rec- ognized that their parent forms were generally not present in circulation [15]. Therefore, whether the in vitro bioactivities of M could pre- dict the in vivo effects and what are the actual molecules working in vivo remain unanswered. Even if the intravenous pharmacokinetics of M and oral pharmacokinetics of [ring- 14 C] labeled M have been previously reported [16, 17], more detailed information of the pharmacokinetics and tissue distribution of M and its metabolites is still lacking. Therefore, this study investigated the pharmacokinetics and tissue distribution of M and magnolol sulfates/glucuronides (M S/G) following intravenous and oral administrations in rats. Materials and Methods ! Plant material The crude drug of the bark of Magnolia officinalis was purchased from a Chinese drugstore in Tai- chung, Taiwan. The origin was identified by Dr. Yu-Chi Hou by microscopic examination, and a voucher specimen (CMU-P-1905-03) was depos- ited in the Graduate Institute of Chinese Pharma- ceutical Sciences, China Medical University, Tai- chung, Taiwan. Abstract ! Magnolol (M) is a polyphenol antioxidant abun- dant in the bark of Magnolia officinalis Rehder & E. Wilson, a popular Chinese herb. To understand the pharmacokinetics and bioavailability of M, Sprague-Dawley rats were intravenously injected with a bolus of M (20 mg/kg) and orally given a single dose and seven doses of M (50 mg/kg). Blood samples were withdrawn via cardiopunc- ture at specific times. Organs including the liver, kidney, brain, lung, and heart were collected at 30 min after the 7th oral dose. The serum and tis- sue specimens were assayed by HPLC before and after hydrolysis with β-glucuronidase and sulfa- tase. The results showed that after intravenous bolus, the systemic exposure of magnolol glucu- ronides (MG) was comparable with that of M while after oral administration, magnolol sul- fates/glucuronides (M S/G) were predominant in the bloodstream. Conversely, M was predominant in the liver, kidney, brain, lung, and heart. Among the studied organs, the liver contained the highest concentrations of M and MG. In conclusion, M S/G was the major form in circulation, whereas M was predominant in the liver, kidney, brain, lung, and heart after oral administration of M; among these organs, the liver contained the highest concentra- tions of M and MG. Abbreviations ! MRT: mean residence time Supporting information available online at http://www.thieme-connect.de/ejournals/toc/ plantamedica Pharmacokinetics, Bioavailability, and Tissue Distribution of Magnolol Following Single and Repeated Dosing of Magnolol to Rats Authors Shiuan-Pey Lin 1 , Shang-Yuan Tsai 1 , Pei-Dawn Lee Chao 1 , Ying-Chen Chen 2 , Yu-Chi Hou 1,3 Affiliations 1 School of Pharmacy, China Medical University, Taichung, Taiwan 2 Institute of Chinese Pharmaceutical Sciences, China Medical University, Taichung, Taiwan 3 Department of Medical Research, China Medical University Hospital, Taichung, Taiwan Key words l " magnolol l " sulfates/glucuronides l " pharmacokinetics l " tissue distribution l " HPLC l " Magnolia officinalis l " Magnoliaceae received February 26, 2011 revised May 2, 2011 accepted May 3, 2011 Bibliography DOI http://dx.doi.org/ 10.1055/s-0030-1271159 Published online June 1, 2011 Planta Med 2011; 77: 1800–1805 © Georg Thieme Verlag KG Stuttgart · New York · ISSN 0032‑0943 Correspondence Dr. Yu-Chi Hou School of Pharmacy, China Medical University No. 91 Hsueh-Shih Road Taichung 40402 Taiwan Phone: + 88 6 4 22 03 10 28 Fax: + 88 6 4 22 03 10 28 hou5133@gmail.com 1800 Lin S-P et al. Pharmacokinetics, Bioavailability, and … Planta Med 2011; 77: 1800–1805 Original Papers Downloaded by: Kaohsiung Medical University. Copyrighted material.